Approximately 90% of HNSCC present high expression of EGFR protein, and cetuximab seemed to be a reasonable targeted therapy for these tumours.41 However, just a small fraction of patients respond to cetuximab, and virtually all responders develop acquired resistance.42 To prolong disease control, it is crucial to identify the changes related to resistance while the tumour is still responsive to cetuximab. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.